DNA Alterations Detected In Plasma Correlate With Lung Tumor Genomic Mutations

NEW YORK (Reuters Health) - Multiple genetic markers detected in plasma match those seen within tumors of patients with lung cancer, in most cases, European investigators report. The results suggest that blood testing may become feasible as a noninvasive strategy for early cancer detection.

“Recent studies have demonstrated the possibility to detect genetic changes in plasma DNA of cancer patients,” Dr. Francesca Andriani, of the Istituto Nazionale Tumori, in Milan, Italy, and colleagues write in the January 1st issue of the International Journal of Cancer. They sought to validate a panel of molecular markers for lung cancer detection in plasma DNA.

The team used three markers -- mutations in p53, inactivation of the FHIT (fragile histidine triad) gene, and microsatellite alterations at four loci on chromosome 3 -- to detect mutations in tumor and plasma DNA of 64 patients with stage I-III non-small-cell lung cancer.

They used direct sequencing of exons 5 through 8 in tumor DNA and plaque hybridization assay and sequencing in plasma DNA to analyze p53 mutations. Allelic losses were assessed using fluorescent PCR in tumor and plasma DNA.

Among the 64 tumor DNA samples, the investigators observed p53 genomic mutations in 26 (40.6%) and the same mutation in 19 plasma specimens.

Microsatellite alterations at FHIT and 3p loci were detected in 40 (62.5%) tumor DNA samples and in 23 (35.9%) plasma samples. Of the 40 patients with microsatellite alterations in tumors, 19 had the identical alteration in plasma DNA.

“When plasma samples were grouped according to alterations found in any genetic markers (FHIT, 3p, p53), tumor-specific changes were detected in 33 of 64 (51.6%) of all patients and in 17 of 29 (58.6%) of stage I patients,” Dr. Andriani and colleagues explain.

“Moreover,” the say, “genetic markers in plasma identified 29 of 45 (64.4%) of all stages and 15 of 22 (68.2%) of stage I patients whose tumors had a detectable alteration at any of the three markers.”

The researchers conclude that the results “provide proof of principle that plasma DNA alterations are tumor-specific in most cases and support blood testing as a noninvasive strategy for early detection.”

Source: Int J Cancer 2004;108:91-96. [ Google search on this article ]

MeSH Headings:Lung Neoplasms: Neoplasms: Neoplasms by Site: Respiratory Tract Neoplasms: Thoracic Neoplasms: Genes, p53: DiseasesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.

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